Electroneutral cation-chloride cotransporters are widely expressed and perform a variety of physiological roles. A novel gene family of five members, encompassing a Na+-Cl- transporter, two Na+-K+-2Cl- transporters and two K+-Cl- cotransporters, encodes these membrane proteins; homologous genes have also been identified in a prokaryote and a number of lower eukaryotes. The cotransporter proteins share a common predicted membrane topology, with twelve putative transmembrane segments flanked by long hydrophilic N- and C-terminal cytoplasmic domains. The molecular identification of these transporters has had a significant impact on the study of their function, regulation and pathophysiology.
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Function and regulation of the insect NaCCC2 sodium transport proteins.
Comp Biochem Physiol A Mol Integr Physiol
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Department of Biology, Kenyon College, Gambier, OH 43050, USA. Electronic address:
NaCCC2 transport proteins, including those from Drosophila melanogaster (Ncc83) and Aedes aegypti (aeCCC2), are an insect-specific clade with sequence similarity to Na-K-2Cl cotransporters. Whereas the Na-K-2Cl cotransporters and other cation-chloride cotransporters are electroneutral, recent work indicates that Ncc83 and aeCCC2 carry charge across membranes. Here, we further characterize the regulation and transport properties of Ncc83 and aeCCC2 expressed in Xenopus oocytes.
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Am J Physiol Regul Integr Comp Physiol
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School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
Na/Cl cotransporter 2 (Ncc2 or Slc12a10) is a membrane transport protein that belongs to the electroneutral cation-chloride cotransporter family. The Slc12a10 gene () is widely present in bony vertebrates but is deleted or pseudogenized in birds, some bony fishes, and most mammals. Slc12a10 is highly homologous to Ncc (Slc12a3 or Ncc1); however, there are only a few reports measuring the activity of Slc12a10.
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Kidney360
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Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Transporters of the solute carrier family 12 (SLC12) carry inorganic cations such as Na and/or K alongside Cl across the plasma membrane of cells. These tightly coupled, electroneutral, transporters are expressed in almost all tissues/organs in the body where they fulfil many critical functions. The family includes two key transporters participating in salt reabsorption in the kidney: the Na-K-2Cl cotransporter-2 (NKCC2), expressed in the loop of Henle, and the Na-Cl cotransporter (NCC), expressed in the distal convoluted tubule.
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Membranes (Basel)
November 2022
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84102, USA.
Loop and thiazide diuretics have been cornerstones of clinical management of hypertension and fluid overload conditions for more than five decades. The hunt for their molecular targets led to the discovery of cation-chloride cotransporters (CCCs) that catalyze electroneutral movement of Cl together with Na and/or K. CCCs consist of two 1 Na-1 K-2 Cl (NKCC1-2), one 1 Na-1 Cl (NCC), and four 1 K-1 Cl (KCC1-4) transporters in human.
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